title: Physiological testosterone retards cardiomyocyte aging in Tfm mice via androgen receptor-independent pathway.
abstract: OBJECTIVE
  To determine whether testosterone modulates markers of cardiomyocytes aging via its classic androgen receptor (AR)-dependent pathway or conversion to estradiol.
  
  
  METHODS
  Male littermates and testicular feminized (Tfm) mice were randomly separated into 4 experimental groups littermate controls (n=8), Tfm mice (n=7), testosterone-treated Tfm mice (n=8), and Tfm mice treated with testosterone in combination with the aromatase inhibitor anastrazole (n=7). Cardiomyocytes were isolated from mouse left ventricles, the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the amount of malondialdehyde (MDA) were measured using colorimetry method, and expression of p16(INK4α) and retinoblastoma (Rb) proteins were detected by Western blotting.
  
  
  RESULTS
  The SOD and GSH-Px enzyme activities of cardiomyocytes were decreased, and the MDA levels and the expression of p16(INK4α) and Rb proteins were increased in Tfm mice compared with control mice. An increase was observed in the activities of SOD and GSH-Px enzyme as well as a decrease in MDA levels and the expression of p16(INK4α) and Rb proteins in the testosterone-treated Tfm mice. After co-treatment with anastrazole in Tfm mice, these improvement were partly inhibited.
  
  
  CONCLUSIONS
  Physiological testosterone replacement can delay cardiomyocyte aging in Tfm mice, an effect that is independent of the AR pathway and in part conversion to estradiol.
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Da
authors.initials: D
authors.lastname: Lei
authors.forename: Gui-Ping
authors.initials: GP
authors.lastname: Zhu
authors.forename: Lei
authors.initials: L
authors.lastname: Hong
authors.forename: Sai-Zhu
authors.initials: SZ
authors.lastname: Wu
mesh_terms: D013734:Androgen-Insensitivity Syndrome / Q000378:metabolism*; D000818:Animals; D016922:Cellular Senescence; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D051379:Mice; D032383:Myocytes, Cardiac / Q000502:physiology*; D011944:Receptors, Androgen / Q000502:physiology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013739:Testosterone / Q000502:physiology*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D011944:Receptors, Androgen; D013739:Testosterone; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase